APEX1 Gene

Name	APEX nuclease (multifunctional DNA repair enzyme) 1
Description	The APEX gene encodes the major AP endonuclease in human cells. It encodes the APEX endonuclease, a DNA repair enzyme with apurinic/apyrimidinic (AP) activity. Such AP activity sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. The AP sites are the most frequent pre-mutagenic lesions that can prevent normal DNA replication. Splice variants have been found for this gene; all encode the same protein. Disruptions in the biological functions related to APEX are associated with many various malignancies and neurodegenerative diseases.[provided by RefSeq, Dec 2019]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n APEX1 (also known as APE1/Ref‐1) is a multifunctional protein that plays a central role in maintaining genome integrity and regulating cellular homeostasis. In its canonical function within the base excision repair pathway, APEX1 incises DNA at apurinic/apyrimidinic (AP) sites generated by oxidized or alkylated bases and—in a related nucleotide incision repair pathway—directly cleaves damaged DNA without the prior action of a glycosylase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition to its essential endonuclease activity, which is critical for cell viability as evidenced by rapid apoptosis upon its depletion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and genetic ablation studies"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", APEX1 also functions as a redox effector. Through redox-dependent regulation of transcription factors (including AP‐1, NF‑κB, p53, and HIF), it modulates the expression of genes involved in proliferation, apoptosis, and differentiation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "and further orchestrates responses to oxidative stress.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, APEX1 facilitates protein–protein interactions that promote efficient hand‐offs in the sequential steps of repair—for instance, by coordinating with DNA glycosylases and repair scaffolds such as XRCC1"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and indirectly enhancing the activity of enzymes like hSMUG1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Its subcellular localization and activity are carefully modulated by post–translational modifications and interactions with other factors (for example, nucleophosmin in the nucleolus) that couple DNA repair with RNA quality control and ribosome biogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Aberrant expression or polymorphic variations in the APEX1 gene have been linked with altered DNA repair capacity and cancer progression. Elevated APEX1 levels have been associated with increased cell proliferation and chemoresistance in certain tumors such as osteosarcoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "and gastric cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", while loss or reduction of its redox effector function—as observed in environments enriched for certain microenvironment‐derived factors—can impair the cellular response to oxidative DNA damage in melanoma cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, APEX1 is a pivotal nexus integrating DNA repair with redox signaling and transcriptional regulation. Its dual role in processing DNA lesions and modulating gene expression is essential not only for safeguarding genomic stability but also for influencing cellular responses in development and disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Laurent Gros, Alexander A Ishchenko, Hiroshi Ide, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The major human AP endonuclease (Ape1) is involved in the nucleotide incision repair pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkh165"}], "href": "https://doi.org/10.1093/nar/gkh165"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14704345"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14704345"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hua Fung, Bruce Demple "}, {"type": "b", "children": [{"type": "t", "text": "A vital role for Ape1/Ref1 protein in repairing spontaneous DNA damage in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2004.12.029"}], "href": "https://doi.org/10.1016/j.molcel.2004.12.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15694346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15694346"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tadahide Izumi, David B Brown, C V Naidu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two essential but distinct functions of the mammalian abasic endonuclease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0500986102"}], "href": "https://doi.org/10.1073/pnas.0500986102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15824325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15824325"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Gianluca Tell, Giuseppe Damante, David Caldwell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The intracellular localization of APE1/Ref-1: more than a passive phenomenon?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Antioxid Redox Signal (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ars.2005.7.367"}], "href": "https://doi.org/10.1089/ars.2005.7.367"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15706084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15706084"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Anna Campalans, Stéphanie Marsin, Yusaku Nakabeppu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "XRCC1 interactions with multiple DNA glycosylases: a model for its recruitment to base excision repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "DNA Repair (Amst) (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dnarep.2005.04.014"}], "href": "https://doi.org/10.1016/j.dnarep.2005.04.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15927541"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15927541"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Bodil Kavli, Ottar Sundheim, Mansour Akbari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "hUNG2 is the major repair enzyme for removal of uracil from U:A matches, U:G mismatches, and U in single-stranded DNA, with hSMUG1 as a broad specificity backup."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M207107200"}], "href": "https://doi.org/10.1074/jbc.M207107200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12161446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12161446"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mengxia Li, David M Wilson "}, {"type": "b", "children": [{"type": "t", "text": "Human apurinic/apyrimidinic endonuclease 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Antioxid Redox Signal (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ars.2013.5492"}], "href": "https://doi.org/10.1089/ars.2013.5492"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23834463"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23834463"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Dong Wang, Meihua Luo, Mark R Kelley "}, {"type": "b", "children": [{"type": "t", "text": "Human apurinic endonuclease 1 (APE1) expression and prognostic significance in osteosarcoma: enhanced sensitivity of osteosarcoma to DNA damaging agents using silencing RNA APE1 expression inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2004)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15210853"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15210853"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yi Qing, Qing Li, Tao Ren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of PD-L1 and APE1 is associated with tumorigenesis and poor prognosis of gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Des Devel Ther (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/DDDT.S75152"}], "href": "https://doi.org/10.2147/DDDT.S75152"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25733810"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25733810"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Amanpreet Kaur, Marie R Webster, Katie Marchbank, et al. "}, {"type": "b", "children": [{"type": "t", "text": "sFRP2 in the aged microenvironment drives melanoma metastasis and therapy resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature17392"}], "href": "https://doi.org/10.1038/nature17392"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27042933"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27042933"}]}]}]}
Synonyms	REF1, HAP1, APE, APEN, APX, APEX, APE1
Proteins	APEX1_HUMAN
NCBI Gene ID	328
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

APEX1 has 12,554 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 135 datasets.

Click the + buttons to view associations for APEX1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

APEX1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by APEX1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of APEX1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of APEX1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of APEX1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of APEX1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of APEX1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of APEX1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving APEX1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of APEX1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of APEX1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of APEX1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of APEX1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of APEX1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of APEX1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with APEX1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with APEX1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of APEX1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of APEX1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of APEX1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of APEX1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of APEX1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing APEX1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing APEX1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing APEX1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing APEX1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with APEX1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with APEX1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing APEX1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of APEX1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with APEX1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with APEX1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with APEX1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by APEX1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for APEX1 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with APEX1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with APEX1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with APEX1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with APEX1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with APEX1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for APEX1 protein from the curated DrugBank Drug Targets dataset.